A Pharmacokinetic and Bioequivalence Study of Savolitinib Tablets in Healthy Chinese Male Volunteers

NCT03860948 | Completed Phase 1

• 1 other identifier: 2018-504-00CH1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, open lebal, single-dose, three-period, crossover clinical study in healthy Chinese male subjects to assess the pharmacokinetics and bioequivalence/bioavailability of two formulation savolitinib tablets.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (5)

• The area under the curve(AUC) of savolitinib

  The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.

  Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

• Maximum observed plasma concentration (Cmax) of savolitinib

  Maximum observed concentration, occurring at Tmax.

  Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

• The time to Cmax (peak time, Tmax) of savolitinib

  The time at which maximum plasma concentration (Cmax) is observed.

  Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

• Half-life (t1/2) of savolitinib

  The time required for the concentration of the drug to reach half of its original value.

  Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

• Bioequivalence of savolitinib

  A term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug.

  Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

Secondary Outcomes (2)

• To observe the safety of healthy volunteers after a single oral dose of savolitinib

  From the first dose to within 12 days after the last dose

• Relative bioavailability of savolitinib

  Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.

Study Arms (2)

Savolitinib Test Preparation

EXPERIMENTAL

The subjects in this arm will receive Test preparation (T). T is dry granulation savolitinib tablets.

Drug: Savolitinib Test Preparation

Savolitinib Reference Preparation

EXPERIMENTAL

The subjects in this arm will receive Reference preparation(R). R is wet granulation savolitinib tablets.

Drug: Savolitinib Reference Preparation

Interventions

Savolitinib Test Preparation DRUG

Test preparation (T): dry granulation savolitinib tablets.

Also known as: HMPL-504, volitinib, AZD6094

Savolitinib Test Preparation

Savolitinib Reference Preparation DRUG

Reference preparation (R): wet granulation savolitinib tablets.

Also known as: HMPL-504, volitinib, AZD6094

Savolitinib Reference Preparation

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must agree to comply with the protocol and Informed consent must be obtained in writing for all subjects;
• Healthy male subjects aged 18 to 45 years inclusive at the time of screening;
• Weight ≥ 50 kg, body mass index (BMI) of 19-26 kg/m2;
• No clinically significant abnormalities or findings in medical history, vital signs, physical examination, 12-lead ECG and laboratory values;
• Males with the ability to have children must commit to adopting reliable contraceptive measures (e.g. condoms, contraceptive sponges, contraceptive gels, contraceptive films, intrauterine devices, contraceptives for oral or injectable intake, subcutaneous implants or other contraceptives) in collaboration with their partners for the duration of the study and for three months after the final dosage.

You may not qualify if:

• History or symptoms of a clinically significant illness in metabolic/ endocrine, liver, kidney, blood, lung, immune system, cardiovascular, gastrointestinal, genitourinary, neurological, or psychiatric systerm in the 3 months before the study, as determined by the investigator;
• History of gastrointestinal surgery, kidney surgery and cholecystectomy, which may potentially affect the absorption or excretion of drugs, as determined by the investigator ;
• History of a severe allergy (for example, certain drug allergy) and acute allergic rhinitis or food allergy within 2 weeks prior to the screening stage;
• Serum albumin \< 35 g/L;
• Hypertention: systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg
• Mean corrected QT interval (QTcF) in electrocardiograms (ECG), males \> 450 milliseconds, or existing factors that may increase the risk of QTc prolongation, such as chronic hypokalemia that cannot be corrected by potassium supplementation, or congenital or familial long QT syndrome or a family history of unexplained sudden death under 40 years of age in first-degree relatives, or use any combination of drugs known to prolong the QT interval and cause torsades de pointes.
• Clinical significant abormal findings in Chest X-ray (posteroanterior position) examination;
• Serum virology positive findings, including HBS Ag, HCV Ab, HIV Ab, or TP Ab;
• Current smoker of more than 10 cigarettes or equivalent / day during past 3 month prior to commencing the study and unable to completely stop smoking during the study;
• Have blood or blood products transfusion within 2 months; or blood donation of more than 250 mL within 1 month or 400 mL within 3 months prior to screening; or planning to donate blood or blood components during the study or within 1 month after the end of the study;
• History of alcohol abuse or drug addiction within one year prior to screening;
• Participation in any other investigational drug clinical study while last dose was administrated within three months prior to the screening.

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

Shanghai Xuhui District Central Hospital

Shanghai, Shanghai Municipality, 200031, China

Location

MeSH Terms

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine

Study Officials

• Jingying Jia

  Shanghai Xuhui District Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 4, 2019
• Study Start: April 16, 2019
• Primary Completion: May 2, 2019
• Study Completion: May 14, 2019
• Last Updated: May 16, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)